The mouse mammary tumor model is extensively used in the study of the etiology and progression of mammary cancer. The viral etiology of mammary tumors in laboratory mice has been well documented; however, mammary tumor viruses (MTVs) have not been isolated from other species. By the use of purified MMTV proteins and antisera prepared against a virus (MC-MTV) which we have recently isolated from Mus cervicolor mice, interspecies RIAs have been developed for the 52,000d and the 36,000d membrane glycoproteins and the 28,000d internal proteins of MTVs. These have been used to detect MTV-related antigens in milks and spontaneous mammary tumors of four distinct rodent species. These studies have identified new biological systems for the study of virus mediated mammary neoplasia. Host-range variants of MTVs have been isolated that can efficiently infect a variety of mammalian cells. MTV-infected cells, including those of murine, rat, feline and human origin now make available substrates for viral cocarcinogenesis studies.